Design, synthesis, and computational studies of phenylacetamides as antidepressant agents

In the present work, a hit molecule obtained from zinc 'clean drug-like database' by systematically performed computational studies was modified chemically to obtain different derivatives (VS1-VS25). Structures of synthesized derivatives were confirmed by IR, H-1-NMR, C-13-NMR, C-13-DEPT, MS, and elemental analysis. All the synthesized compounds were biologically evaluated for their antidepressant activity by using tail suspension test and forced swimming test in albino mice. All these derivatives showed moderate to good antidepressant activity. The most potent compound (VS25) among the synthesized compounds showed better antidepressant potential than the standard drugs moclobemide, imipramine, and fluoxetine. To understand the time-dependent interactions of this most active compound with MAO-A molecular dynamics was carried out and reported here. Additionally, acute oral toxicity was performed for the most active compound as per OECD guidelines.

Automated summary

In this study, a hit molecule with antidepressant activity was discovered and modified chemically to obtain different derivatives. The synthesized compounds showed moderate to good antidepressant activity, with the most potent compound exhibiting better potential than standard drugs. Molecular dynamics and acute oral toxicity tests were also performed.